Our studies now have progressed through the treatment of five consecutive patients with breast adenocarcinoma who relapsed while undergoing conventional therapy. Preliminary findings showed antitumor effects in four of five patients treated. In addition we were able to simplify the plasma delivery system as well as modify the toxicity while still retaining tumor necrolytic changes. Analysis of the effluent has revealed that high molecular weight C1q binding material is the predominant material emerging from the column. The postperfusion fractions are capable of inducing chemiluminescence and enzyme release from canine neutrophils. Confirmatory clinical trials are scheduled to commence at the Frederick Cancer Center. The significance of this work is that we have now brought a very crude therapeutic system to refinement and defined proper conditions for its clinical use while markedly simplifying the system technically. Hence, the system has become convenient to use and safe for further clinical trials. Moreover, a predictable tumor inflammatory response may be produced by each treatment. Our present plan is to continue to identify, isolate and purify the major reactants generated in sera after contact with immobilized protein A. With these reactants as prototypes, we plan to prepare each of them in large quantities utilizing more efficient physicochemical techniques. Each of these will be tested individually in our preclinical canine program. With these new instruments in hand, we expect to improve the tumoricidal activity, reduce the toxicity and, hence, provide a greater margin of safety and efficacy for this system when we eventually apply it to treatment of patients with cancer.